Running wheel activity attenuates the effects of exogenous opiates: Implications for the endogenous opioid system

This series of experiments explored the effects of exercise on opiate drug action. Animals running in running wheels for three weeks were significantly less sensitive to the antinociceptive effects of morphine and M6G and recovered moire quickly from morphine- and M6G-induced antinociception than inactive rats. Area under the curve analysis after the administration of 10 mg/kg morphine or 5 mg/kg M6G showed that the peak magnitude and overall duration of antinociception were lower in the active animals than the inactive animals. Morphine and M6G were significantly less antinociceptive after PAG administration in the active animals than the inactive animals after the administration of the highest dose tested (20 mug and 1 mug respectively). Part II explored the effects of running wheel activity on the development of tolerance and hyperphagia after repeated morphine administration. The active animals were significantly more sensitive to the hyperphagic effects of morphine than the inactive animals on the first day of drug administration. Chow intake was significantly greater than saline levels in the active animals after 1, 7 and 10 days of drug administration and after 9 days of drug abstinence and in inactive animals after 7 and 10 days of drug administration. Similarly, active animals showed significantly less antinociception than the inactive animals on day 1. Inactive animals significantly decreased their antinociceptive response after 7 days of drug administration while there were no significant reductions in antinociception in the active animals. Corticosterone levels in the active animals were slightly greater than the inactive animals and the active animals were more sensitive to painful stimuli than the inactive animals. There were no differences in the estrous cycles of the active and inactive animals. Chronic beta endorphin administration partially mimicked the effects of running wheel activity on morphine antinociception. Running and chronic treatment with 7.5 mug/day beta endorphin resulted in decreased morphine antinociception compare with controls and 2.5 mug/day beta endorphin treated animals, however; the running animals recovered more rapidly than all of the other treatment groups. The results of these experiments support the hypothesis that cross-tolerance develops between morphine and endogenous opioids released during running wheel activity.